Substance 33, also known as VR, was developed into a binary Novichok agent as part of the U.S.S.R.’s chemical weapons program. The program also created nerve agents such as A-230, A-232 and A-234, some of which became Novichok agents.

Substance 33, also known as VR, was developed into a binary Novichok agent as part of the U.S.S.R.’s chemical weapons program. The program also created nerve agents such as A-230, A-232 and A-234, some of which became Novichok agents.

Chemical weapons experts have identified the nerve agent used in the attempted murder of a former Russian double agent living in the U.K. It is part of a family of compounds known as Novichok agents that were developed in a Cold War-era weapons program in the former U.S.S.R. Russia now faces questions about its involvement in the attack, and indeed whether it has violated the Chemical Weapons Convention.

The nerve agent was used against Sergei Skripal, previously a Russian military intelligence officer who was convicted of leaking secrets to the U.K. He was released in 2010 and settled in Salisbury, England, where he and his daughter Yulia were poisoned on March 4.

“It is now clear that Mr. Skripal and his daughter were poisoned with a military-grade nerve agent of a type developed by Russia,” U.K. Prime Minister Theresa May said on Monday, March 12, citing work by investigators at the U.K.’s Defence Science & Technology Laboratory at Porton Down. May said that it was “highly likely that Russia was responsible”, although Russia has denied any involvement in the attack.

Novichok agents are organophosphorus compounds, similar to sarin and VX, which inhibit the enzyme acetylcholinesterase and cause a biochemical logjam that cripples the nervous system. Symptoms range from sweating and twitching to seizures and an inability to breathe. The U.K. has not disclosed the specific Novichok agent used against the Skripals.

“The U.S.S.R. is the only country to have developed and produced these [Novichok] agents,” says Jean Pascal Zanders, an independent consultant who was previously a senior research fellow at the European Union Institute for Security Studies. “It’s almost as though the Russians are sending a message to the West that they can reach anywhere, whenever they like.”

The newcomers

Much of what is publicly known about Novichok agents comes from Vil Mirzayanov, an analytical chemist who worked for the State Research Institute of Organic Chemistry and Technology (GosNIIOKhT), a notorious chemical weapons laboratory. Mirzayanov developed methods to detect nerve agents created and tested in the U.S.S.R.’s chemical weapons facilities. His techniques would be used to monitor the environment for any traces of the agents that might reveal the labs’ activities to foreign intelligence services.

In the late 1980s, Mirzayanov’s analytical techniques revealed that nerve agents were befouling the air and water around one of these facilities, posing a major health risk. So he went public, revealing details of the U.S.S.R.’s chemical weapons program to Moscow News in 1992. Officials arrested and imprisoned Mirzayanov, but eventually dropped the case against him. In 1995, he immigrated to the U.S., where he subsequently wrote a book about his experiences, titled “State Secrets: An Insider’s Chronicle of the Russian Chemical Weapons Program.”

￼Firefighters secure a tent over the bench where Skripal and his daughter were found unconscious.

￼Firefighters secure a tent over the bench where Skripal and his daughter were found unconscious.

The book documents the U.S.S.R.’s search for new chemical weapons—the “Foliant” program—from the early 1970s until the early 1990s. That program had several goals. It aimed to develop nerve agents that could not be stopped by the chemical protective gear available to NATO soldiers at the time. It also looked for chemical agents that were safer to handle and undetectable in conventional analytical tests. One of the key approaches used to achieve the safety and evasion goals involved so-called binary agents—chemical weapons that could be produced immediately before they were deployed, by combining simple and innocuous precursors. “They would have used precursors more frequently present in the chemical industry,” says Ralf Trapp, a consultant chemist and toxicologist who previously worked for the Organisation for the Prohibition of Chemical Weapons (OPCW).

According to writings by Jonathan B. Tucker, a chemical weapons expert, the first binary formulation developed under Foliant was used to make Substance 33, also known as VR. This compound is very similar to the more widely known VX, differing only in the alkyl substituents on its nitrogen and oxygen atoms. “This weapon was given the code name Novichok,” Tucker wrote in “War of Nerves: Chemical Warfare from World War I to Al-Qaeda.” Novichok is the Russian word for ‘newcomer’.

In “State Secrets,” Mirzayanov tells that the program also developed a range of compounds based on the phosphorus-oxygen-fluorine core of older nerve agents like sarin and soman. By substituting the O-alkyl group in these compounds for an amidine, Foliant scientists created a molecule dubbed A-230. Some five to eight times more poisonous than VX, it was subsequently adopted as a chemical weapon by the Soviet Army. Further variations on this theme produced A-232, which had a similar toxicity to Substance 33 but was much more volatile; and its ethoxy analogue, A-234.

GosNIIOKhT researchers then developed a binary formulation that would produce A-232 (or something very close to it) on demand. This was designated Novichok-5. “Both precursor chemicals had legitimate industrial uses,” Tucker wrote, “so they could be produced at plants ostensibly designed to manufacture agricultural fertilizers or pesticides.” In 1993, Foliant spawned another binary—Novichok-7—that was reportedly just as potent.

Mirzayanov writes that the U.S.S.R. produced a few tons of Novichok-5, and tens of tons of Novichok-7. According to Tucker, the U.S.S.R. carried out open-air tests of Novichok-5 in the early 1990s on the Ustyurt Plateau, a desert area close to the border of present-day Kazakhstan and Uzbekistan. Györgyi Vásárhelyi and László Földi of the National University of Public Servicehave reported that Novichok-5 and -7 act very rapidly, penetrating the skin and respiratory system.

Plausible explanations

Mirzayanov’s account only provides a snapshot of the Foliant program. Indeed, other scientists have proposed many different formulas for Novichok agents, including a series that incorporates a myriad of dihaloformaldoxime groups. Some estimate that over 100 nerve agents were developed under Foliant, although it is unclear how many of them evolved into binary agents.

Novichok agents are not specifically listed in the schedules of the Chemical Weapons Convention (CWC), says Zanders, because “they only became public after the treaty negotiations had been concluded.” But that does not amount to a loophole that would allow their use, because the CWC places a blanket prohibition on the manufacture of any toxic chemical intended to be a weapon. “It covers any toxic chemical, be it past, present, or future,” says Zanders. Russia has been a party to the convention since late 1997, and the Novichok agents “should have been declared to the OPCW, even if they don’t appear in the schedules,” says Zanders.

Prime Minister May has said that there are only two plausible explanations for the attack on the Skripals: “Either this was a direct act by the Russian State against our country, or the Russian government lost control of this potentially catastrophically damaging nerve agent and allowed it to get into the hands of others.” Either of those scenarios would mean that Russia is in breach of the CWC, says Zanders.

May has demanded an explanation from Russia, along with a complete disclosure of the Novichok program to the OPCW. Meanwhile, the executive council of the OPCW is holding a scheduled meeting in The Hague today. Zanders expects that the Novichok attack will be high on the agenda.

CORRECTION: This story was updated on March 15, 2018, to specify when Russia became a party to the Chemical Weapons Convention.

Being OP compounds, are the Novichok agents treatable by atropine and oximes (and benzodiazepine anticonvulsants)? Do we know the aging periods for AChE binding? Or do they have other pathophysiological mechanisms besides OP effects? I am a physician, and would like to know what medical countermeasures should be given besides airway and ventilator support.

I understood that the binding of these agent to AChE was more or less, and in practical terms, permanent, with very low Km values. Atropine and pralidoxime can only help, but by the time it is administered, it's usually too late. An interesting hypothesis (which I'm sure someone has looked at) - would it be possible to administer AChE itself? I doubt you can buy it off the shelf, but given the administration of enzymes has some clinical history (eg. aspariginase - to take a very old example), would it be worth a shot?

Sorry, should have mentioned there is a mechanism behind the effectively permanent deactivation of AChE - the enzyme and its bound inhibitor eventually cause the AChE to 'age' and this is effectively irreversible. I'm not sure what the aging time is, but I don't believe it is very long. These agents work as competitive inhibitors, binding to the same active site as ACh, but the binding of the agent induces a conformational change in the enzyme, rendering it almost completely inactive.

If Prime Minister May said something, it does not mean it is true. They must present full report including chemical analyses and comparison with a known standard in order to prove that the substance is "Novichok". If UK has such a "standard", they must have an exact chemical formula and therefore they are able to produce this substance in UK. Otherwise, they can speculate who produced this substance and what is this substance till the end of days. We are scientist and only scientific method is valid, not what Prime Minister has to say.

Is it conceivable for a competent chemist who has seen the formula for such a nerve agent to successfully guess an appropriate binary formula and procedure to make a small amount? If the raw materials are commercially available, could a chemist working for any of a number of other military or secret services produce the material?

Yes. Lots of things are possible with the proper investment of resources.

Based on the chemistry involved a lot of those compounds look unstable (heat/moisture/light/oxygen sensitive).

Also, manufacturing stuff like this in a laboratory is, ironically, much more difficult in the laboratory than it is in a factory with dedicated, connected, reactors/purification systems.

Also making it either requires a big glovebox with robotic arms or that you wear scuba gear and a hazmat suit. Its also highly specialized chemistry that has basically no application outside of pesticides and chemical weapons, so its not the type of thing that any old organic chemist who got their PhD doing total synthesis or studying catalysts or making organic semiconductors would be able to readily jump into.

I wonder why we do not hear of the various chemical and biological agents that were also created by the West during and after the cold war? Is not objective reporting a balanced look at both sides of a story?

Francis, the story is about a particular class of chemical agents, said to be used by Russia to kill someone, and said to be developed by Russia. The West is not accused of having recently used a nerve agent to kill someone, so why would you expect this article to address chemical agents previously developed by the West? Russia is accused of having recently violated an international treaty through the use of one of these compounds. The West is not.

Accused by whom? accused based on what evidences? I can accuse UK. I do not have evidences. Yet, presumption of being innocence looks to be forgotten, so let me accuse UK and now I would like to ask same question. Are they able to produce such nerve agents in "Porton Down", where VX was developed? Many western countries are able to produce this and many other agents like this. Should I accuse them all? Better think, who is taking benefits from the case. We all read detective stories. We are all highly educated people. Just ask your self "Cui prodest?"

Yes, Russia is a prime suspect. This could be, as stated, a warning, just as Putin warned he has nukes that can hit Florida.

But there is at least one other possible source-a third party or country who has reinvented the product on his own using available info. But we also need a motive-for anyone-why would Russia decide to kill these two now after years in England? Why would a third party?

Question 1: How reliable are the tests that were used to identify the toxicant in the British labs?

Question 2: How did Russians do their 'open air tests" to determine toxicity and exposure route? I just wonder who volunteered!!!!

These are not complex substances. It is not impossible to imagine that knowing structure any organic chemist would be able to produce it. For instance, when sarin (or tabun?) was used in Tokyo subway in later 20th century, nobody was suggesting that German government of the day was responsible for providing it. Moreover, substances of this kind are not very stable, and while stored in a forgotten corner of a warehouse, after half of a century the containers may contain decomposition products only. So it looks like the "third party" involvement suggested above is a possibility. It may require Hercule Poirot to discover who would have a motive to using it.

I am amazed how far reaching conclusions, even verdicts are made based on the scarce information available. Structure(s) have not been disclosed, investigation is still ongoing yet some people claim to know whodunit.

"It is a capital mistake to theorize before one has data. Insensibly one begins to twist facts to suit theories, instead of theories to suit facts."

The capacity of humans to make extremely destructive weapons is staggering! Thanks for the intelligent description of the history of these compounds, and their associated chemistry - most interesting for people like me with chemistry backgrounds. I guess a minor consolation is that these substances are so incredibly toxic, your typical terrorist outfit would be too stupid/careless to handle them, but the possibility of binary Novichok anticholinesterase chemicals is absolutely frightening. I would have initially thought that the precursors (particularly those to create the fluorophosphonate moiety) would be tracked, but it sounds like they've found a way to avoid these watched chemicals and use untracked items instead. Very scary. I also don't understand why the UK left itself open to Russian criticism by not sharing the analysis they have done - while the Russians would have disagreed with the results, they at least couldn't use the excuse they have never seen them.

Anyone with expertise in chemistry can produce sarin.
Binary Chemical weapons pose another problem if the 2 chemicals are commonly used industrial substances.
As I understand it, the binary components of chemical weapons were not necessarily destroyed, particularly, if they have other industrial uses.
I don't think this nerve agent is harder to produce than a pesticide.
Plausibly, this does sound like a rogue operation, or a personal vendetta.

A story as told to me: A small African country, with a population of less than 10 million, sends a big delegation to Moscow. They are in absolute awe of the technological might of the Soviet Union. After a couple of glasses(or bottles) of vodka, they confess feeling absolutely worthless. They say- "We know you guys think of us as Monkeys" - but we are going to evolve and improve. Russians deny this and insist that they believe in human equality. A KGB colonel then asks, Can you give us a few hundred monkeys? We need them for scientific experiments. I dont know whether monkeys were actually sent to the Soviet Union...

I find it very interesting that Russia would use a weapon such as a Novichok agent that could be easily tied to their chemical arsenal. The only detail more interesting than the agent used, is the motive behind the attempted assassination of Mr. Skripai and his daughter. I question why Russia would attempt to kill a former spy that they released almost eight years ago, and risk an international incident with the United Kingdom?

If as is claimed by George Galloway, presumably on reliable intelligence, that contamination occured at, and not later than, their occupation of their home address, it is clear that there was significant time delay between exposure and physiological symptoms and signs developing. In other words at least the time between them occupying their house being descovered on the park bench. If the released video, given considerable publicity by news outlets, can be believed, they were perfectly healthy and unaffected at 4.47 pm less than half an hour before they were spotted in a semi-comatose condition. Now given the fact that one of the characteristics of 'Novichok 5 and 7' is they 'act very quickly', some explanation for the delayed response should be provided, either chemical or technological. However the fact that traces of the substance were apparently located at the residence and other properties, presumably carried there by the Skripals, as a result of general contamination of their clothing, an explanation for the delayed effect seems even harder to explain.

Most competent chemists could produce these agents without difficulty in a lab I would imagine. Doing so without poisoning oneself would be more challenging. Dosing one to a targeted individual would, I would expect, require a mmoderately sophisticated device, perhaps akin to a modified asthma inhaler.

As a chemist the 'only' thing I do not understand why the agents shown above - and the structures widely circulated elsewhere - are called 'binary' agents. Is it known from the chemical literature what the two apparently stable precursors for these could be?

Can anyone comment on the likely Half-Life of Novichock agents and/or their binary precursors?

If this/these agent(s) are only likely to remain usable for a matter of a couple of years (which I understand usual for similar organophosphate pesticides), it would rather kill the idea of "leftover" material from the old Soviet Union being used, and raise a more troubling probability of ongoing manufacture in Russia.

"Chemical weapons experts have identified the nerve agent used in the attempted murder of a former Russian double agent living in the U.K." O.K. .... Which one ? Nowhere in the article does it say exactly which nerve agent (or mixtures thereof if applicable) was actually used. "Some estimate that over 100 nerve agents were developed under Foliant, although it is unclear how many of them evolved into binary agents." This is fine and dandy and also available on Wikipedia, but does nothing to clarify things. So which of the hundreds of possible nerve agents was actually used??? I assume spectral evidence of this is what the Russians want to see.